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何文明, 戴婷, 陈炯, 王建安. 2019: LECT2抑制Apoe-/-小鼠体内动脉粥样硬化的发展. 动物学研究, 40(4): 317-323. DOI: 10.24272/j.issn.2095-8137.2019.030
引用本文: 何文明, 戴婷, 陈炯, 王建安. 2019: LECT2抑制Apoe-/-小鼠体内动脉粥样硬化的发展. 动物学研究, 40(4): 317-323. DOI: 10.24272/j.issn.2095-8137.2019.030
Wen-Ming He, Ting Dai, Jiong Chen, Jian-An Wang. 2019: Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice. Zoological Research, 40(4): 317-323. DOI: 10.24272/j.issn.2095-8137.2019.030
Citation: Wen-Ming He, Ting Dai, Jiong Chen, Jian-An Wang. 2019: Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice. Zoological Research, 40(4): 317-323. DOI: 10.24272/j.issn.2095-8137.2019.030

LECT2抑制Apoe-/-小鼠体内动脉粥样硬化的发展

Leukocyte cell-derived chemotaxin 2 inhibits development of atherosclerosis in mice

  • 摘要: 白细胞衍生趋化因子2(LECT2)是一种多功能的肝细胞因子,参与许多疾病的调节。然而,它在动脉粥样硬化(AS)中的作用仍不清楚。在本研究中,我们选取6周龄的雄性C57BL/6小鼠8只和Apoe-/-小鼠16只。C57BL/6小鼠作为空白对照组给予普通饲料并皮下注射PBS,Apoe-/-小鼠给予高脂饲料以建立AS模型,并随机分为AS组和LECT2组,AS组皮下注射PBS,LECT2组皮下注射LECT2,干预15周后处死小鼠,采集血液样品及病理标本,用油红O和HE染色观察AS斑块的形态及面积,用ELISA法测定血清总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白水平,用ELISA法和qRT-PCR法检测TNF-α,IL-1β,IL-8,MCP-1和MMP-1的血清浓度及mRNA表达水平,通过免疫组化染色检测巨噬细胞标志物CD68,内皮细胞标志物CD31和血管平滑肌细胞标志物α-SMA。结果显示与AS组相比,LECT2组斑块面积减少(P<0.01),血清中的总胆固醇(P<0.05)、甘油三酯(P<0.01)和低密度脂蛋白浓度(P<0.05)降低,TNF-α,IL-1β,IL-8,MCP-1和MMP-1的血清浓度及mRNA表达减少(P<0.05)。此外,LECT2组的AS斑块中CD68含量减少(P<0.05),α-SMA的含量增加(P<0.01)。总之,LECT2可以降低血清总胆固醇浓度,减轻炎症反应,从而抑制AS的发展。

     

    Abstract: Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditions. However, its role in atherosclerosis remains undefined. In this study, we administered vehicle or LECT2 to male Apoe-/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8, IL-1β, and TNF-α were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-α, IL-1β, IL-8, MCP-1, and MMP-1 concentrations were measured by enzyme-linked immunosorbent assay. CD68, CD31, and α-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immunostaining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-α, IL-8, and IL-1β mRNA abundance. Furthermore, LECT2 decreased CD68, but increased α-SMA in atherosclerotic lesions, suggesting an increase in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.

     

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